Using magnetic resonance (MR) imaging and morphometric techniques, groups of patients with Alzheimer's disease (AD) and Huntington's disease (HD) were compared with a large group of normal control subjects. Measures of volume loss in specific subcortical nuclei and eight cortical regions as well as an index of white matter abnormality were obtained. Results indicated expected widespread cortical volume reductions in AD, which were especially severe in mesial cortices; but comparable reductions were present in subcortical structures, particularly the thalamus. In HD, the greatest reductions were in striatal structures, but significant abnormalities were also detected in the thalamus and inferior cortical areas, especially in mesial temporal lobe structures. Significant degeneration in white matter was present in both groups, but was more dramatic in the HD patients. The significant diencephalic reduction in AD may make an important contribution to early memory deficits in the disorder, which are usually attributed to hippocampal damage. Similarly, damage to both the thalamus and mesial temporal lobe structures may play a role in the memory deficits of HD.